Supersaturation-Limited and Unlimited Phase Spaces Compete to Produce Maximal Amyloid Fibrillation near the Critical Micelle Concentration of Sodium Dodecyl Sulfate.

Although various natural and synthetic compounds have been shown to accelerate or inhibit the formation of amyloid fibrils, the mechanisms by which they achieve these adverse effects in a concentration-dependent manner currently remain unclear. Sodium dodecyl sulfate (SDS), one of the compounds that has adverse effects on fibrillation, is the most intensively studied. Here we examined the effects of a series of detergents including SDS on the amyloid fibrillation of ß2-microglobulin at pH 7.0, a protein responsible for dialysis-related amyloidosis. In all the detergents examined (i.e., SDS, sodium decyl sulfate, sodium octyl sulfate, and sodium deoxycholate), amyloid fibrillation was accelerated and inhibited at concentrations near the critical micelle concentration (CMC) and higher than CMC, respectively. The most stable conformation changed from monomers with a ß-structure to amyloid fibrils with a ß-structure and then to α-helical complexes with micelles with an increase in detergent concentrations. These results suggest that competition between supersaturation-limited fibrillation and unlimited mixed micelle formation between proteins and micelles underlies the detergent concentration-dependent complexity of amyloid fibrillation.

Heparin-induced amyloid fibrillation of ß2 -microglobulin explained by solubility and a supersaturation-dependent conformational phase diagram.

Amyloid fibrils are fibrillar deposits of denatured proteins associated with amyloidosis and are formed by a nucleation and growth mechanism. We revisited an alternative and classical view of amyloid fibrillation: amyloid fibrils are crystal-like precipitates of denatured proteins formed above solubility upon breaking supersaturation. Various additives accelerate and then inhibit amyloid fibrillation in a concentration-dependent manner, suggesting that the combined effects of stabilizing and destabilizing forces affect fibrillation. Heparin, a glycosaminoglycan and anticoagulant, is an accelerator of fibrillation for various amyloidogenic proteins. By using ß2 -microglobulin, a protein responsible for dialysis-related amyloidosis, we herein examined the effects of various concentrations of heparin on fibrillation at pH 2. In contrast to previous studies that focused on accelerating effects, higher concentrations of heparin inhibited fibrillation, and this was accompanied by amorphous aggregation. The two-step effects of acceleration and inhibition were similar to those observed for various salts. The results indicate that the anion effects caused by sulfate groups are one of the dominant factors influencing heparin-dependent fibrillation, although the exact structures of fibrils and amorphous aggregates might differ between those formed by simple salts and matrix-forming heparin. We propose that a conformational phase diagram, accommodating crystal-like amyloid fibrils and glass-like amorphous aggregates, is important for understanding the effects of various additives.

Approach to novel functional foods for stress control 2. Microarray assessment of exercise in healthy volunteers.

DNA microarray was used to measure stress response by exercise in peripheral blood leukocytes. Aerobic exercise did not alter mRNA pattern or urinary secretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Strenuous exercise increased urinary secretion of 8-OHdG and altered mRNA pattern in microarray. These results suggest that moderate exercise, i. e. aerobic exercise, did not show any change in 8-OHdG, an oxidative stress marker, or mRNA expression in the leukocytes, which might reflect whole body neurohormanal changes. In addition, strenuous exercise produced quite different expression pattern from those of psychological stress.